Our overall objective is to develop and exploit 15N labeling of rats for quantitative global analysis of signal transduction pathways in the brain. Signal transduction is a key elicitor of a diverse array of functions in the brain that impacts different behaviors. Technology to analyze 15N labeled rat brain proteins to determine quantitative changes in protein phosphorylation provides a means to globally study the activation or suppression of signaling pathways. The ability to perform these studies on discrete sections of the brain will allow the study of brain regions believed to be important in specific behavioral phenotypes. In this project, we will develop the means to quantitatively measure protein phosphorylation in discrete regions of the rat brain using animal models of schizophrenia. Our hypothesis is 15N metabolic labeling of rodents can be used to study signal transduction processes involved in brain dysfunction. The long term goal is to develop methods and technologies to study affective disorders, a health issue for roughly 20 million Americans (5-7% of the population). PUBLIC HEALTH RELEVANCE: Approximately, 20 million Americans are stricken with affective disorders of some type. This research will help establish approaches for examining the molecular processes associated with these disorders. A fundamental understanding of these processes will help the development of therapeutics to alleviate the symptoms associated with affective disorders such as schizophrenia, psychosis, biopolar disorder, and depression.